Major histocompatibility complex class I presentation of exogenously acquired minor alloantigens initiates skin allograft rejection.
Major histocompatibility complex (MHC) class I molecules present peptides from endogenous proteins. However, in some cases class I-restricted peptides can also derive from exogenous antigens. This MHC class I exogenous presentation could be involved in minor histocompatibility antigen (mHAg)-disparate allograft rejection when donor alloantigens are not expressed in graft antigen-presenting cells (APC) that initiate the rejection mechanism. Here we addressed this question by using a skin graft experimental model where donors (H-2b or H-2d Tg beta-gal mice) expressed the mHAg like beta-galactosidase (beta-gal) in keratinocytes but not in Langerhans' cells (LC) which have an APC function. Rejection of Tg beta-gal skin by a beta-gal-specific CD8 cytotoxic T lymphocyte (CTL) effector mechanism should require presentation by donor and/or recipient LC of MHC class I-restricted peptides of exogenous beta-gal shed by keratinocytes. Indeed, our results showed that 1) H-2b Tg beta-gal skin was rejected by H-2bxs and H-2bxd recipients; 2) rejection was mediated by beta-gal-specific CD8+ CTL effectors; and 3) H-2bxd mice having rejected H-2b Tg beta-gal skin generated beta-gal-specific CTL restricted by H-2b and H-2d class I molecules and rejected subsequently grafted H-2d Tg beta-gal skin in an accelerated fashion, demonstrating that recipient LC have presented exogenous beta-gal-derived MHC class I epitopes. These results lead to the conclusion that MHC class I exogenous presentation of donor mHAg can initiate allograft rejection.
Oukka
M
M
INSERM Unité 267, Villejuif, France.
Galou
M
M
Belkaid
Y
Y
Tricotet
V
V
Riche
N
N
Reynes
M
M
Kosmatopoulos
K
K
D000818:Animals; D017951:Antigen Presentation; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D016038:Skin Transplantation; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D007519:Isoantigens